1. Field of the Invention
This invention generally relates to cells derived from adipose tissue, and more particularly, to adipose-derived regenerative cells (e.g., stem and/or progenitor cells), methods of using adipose-derived regenerative cells, compositions containing adipose-derived regenerative cells, and systems for preparing and using adipose-derived regenerative cells which are used to augment fat transfer.
2. Description of Related Art
Fat transfer is a relatively common cosmetic, therapeutic and structural procedure involving the harvest of adipose tissue (fat) from one location and re-implantation in another location (Coleman 1995; Coleman 2001). While being largely used for repair of small cosmetic defects such as facial folds, wrinkles, pock marks and divots, fat transfer has also been used cosmetically in breast augmentation and reconstruction (Bircoll and Novack 1987; Dixon 1988). Augmentation of the buttocks has also been performed using fat transfer approaches (Cardenas-Camarena, Lacouture et al. 1999; de Pedroza 2000; Peren, Gomez et al. 2000).
Existing fat transfer methods, however, are associated with substantial side effects including infection (Castello, Barros et al. 1999; Valdatta, Thione et al. 2001) and calcifications and scarring which can interfere with mammography and other breast imaging modalities (Huch, Kunzi et al. 1998). Current fat transfer methods are also frequently associated with inconsistent engraftment, wherein for example the implanted material is fully or partially resorbed or is replaced by scar tissue (Eremia and Newman 2000). In breast augmentation mammoplasty, for example, use of fat tissue often causes loss of function of the tissue which can be attributed in part to necrosis of implanted fat tissue during the time it takes for new blood vessels to form and feed the implant (Saunders, Keller et al. 1981; Eppley, Smith et al. 1990; Nishimura, Hashimoto et al. 2000). Similarly, for the long-term correction of soft tissue defects, numerous materials, including autologous fat, have been employed for the filling of scars, wrinkles, and other soft tissue defects (Coleman 2001; Maas and Denton 2001). As described above, however, these adipose tissue transplants also suffer from a lack of neovascularization and necrosis.
Autologous fat transfer has also been applied in non-cosmetic clinical settings where a soft tissue filler or support structure is required. One example is stress urinary incontinence in which the transplanted fat is intended to support the urethral wall and urinary sphincter structures (Palma, Riccetto et al. 1997; Lee, Kung et al. 2001). However, the lack of durability of the transplanted fat has prevented widespread acceptance of this technique. A similar approach has been used in fecal incontinence, which is another sphincter disorder (Shafik 1995; Bernardi, Favetta et al. 1998). Other examples where fat transfer has been applied in non-cosmetic clinical settings include vocal cord paralysis, vocal atrophy, intubation trauma, and post-hemilaryngectomy defects, and vocal implantation (Koufman 1991; Mikaelian, Lowry et al. 1991; Hsiung, Woo et al. 2000; Perie, Ming et al. 2002), repair of soft tissue defects caused by irradiation (Jackson, Simman et al. 2001) and war injury (Ghobadi, Zangeneh et al. 1995), in lumbar disc surgery (Bernsmann, Kramer et al. 2001; Kanamori, Kawaguchi et al. 2001), and repair of atrophied tissue in the plantar foot pad (Chairman 1994; Lauf, Freedman et al. 1998). All of these approaches have encountered the problems described above for cosmetic applications.
A number of groups have looked at ways to supplement the graft in such a way as to improve long-term survival and retention. One group has reported results using a serum-free cell culture medium to enhance graft survival in an animal model (Ullmann, Hyams et al. 1998) while others have shown that augmenting transferred tissue with growth factors can enhance graft viability in another model system (Eppley, Snyders et al. 1992; Yuksel, Weinfeld et al. 2000; Yuksel, Weinfeld et al. 2000).
A different approach has been proposed by Schoeller et al. in which adipocyte precursor cells are embedded in fibrin glue and then implanted in the hope that the cells survive and generate new adipose tissue from scratch (Schoeller, Lille et al. 2001). Others have used a similar approach involving seeding artificial polymers with these cells (Patrick, Chauvin et al. 1999). Problems associated with these approaches are that the approaches may bring only one component of adipose tissue (the adipocyte) leaving new blood vessel production (angiogenesis) to endogenous mechanisms. Further, given the limited self-renewal capacity of pre-adipocytes they may be unable to deliver long-term production of adipocytes.
Accordingly, there remains a need for improved methods of administering adipose tissue to patients which reduces the problems associated with existing methods.